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Effect of activation on adhesion of flowing neutrophils to cultured endothelium: time course and inhibition by a calcium channel blocker (nitrendipine)
Author(s) -
Perry I.,
Buttrum S.M.,
Nash G.B.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb14011.x
Subject(s) - nitrendipine , nifedipine , umbilical vein , cd18 , adhesion , chemistry , endothelium , calcium channel , pharmacology , calcium channel blocker , chemotaxis , calcium , immunology , endocrinology , integrin , in vitro , biochemistry , medicine , receptor , organic chemistry
1 Adhesion of neutrophils to vascular endothelium plays an important role in inflammation and thrombosis. Modulation of adhesion may be therapeutic in these conditions. 2 A flow model was used to quantify adhesion of neutrophils to human cultured umbilical vein endothelial cells. The time course of the neutrophil response to activation by N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP, 10 −7 m ) was studied and the inhibitory effects of the calcium‐channel blockers, nitrendipine and nifedipine, were investigated. 3 Neutrophils adhered firmly to the endothelial cells without rolling, but initial attachment was highly dependent on shear stress; doubling the stress from 0.05 to 0.1Pa decreased the number of neutrophils adhering by over 80%. 4 Adhesion rapidly increased after activation of neutrophils by fMLP, peaking at 1–3 min post‐treatment, and then decreased over the next 10–12 min. A monoclonal antibody to the β2‐integrin component CD18 inhibited adhesion by over 80% for activated or unactivated cells. 5 The Ca‐channel blocker, nitrendipine, but not nifedipine, significantly inhibited the fMLP‐induced increase of adhesion in a dose‐dependent manner (10 −8 to 10 −6 m ). Dihydropyridines may be useful agents for modifying neutrophil function.